|LETTER TO THE EDITOR
|Year : 2022 | Volume
| Issue : 1 | Page : 144-148
A hospital-based cross-sectional study on assessment of ER, PR, and Her2 status in breast cancer patients from tertiary-care hospital of rural Maharashtra
Kailas D Datkhile1, Anand K Gudur2, Rashmi A Gudur2, Suresh J Bhosale3
1 Department of Molecular Biology and Genetics, KIMSDU, Karad, Maharashtra, India
2 Department of Oncology, KIMSDU, Karad, Maharashtra, India
3 Department of Surgery, KIMSDU, Karad, Maharashtra, India
|Date of Submission||25-Jan-2021|
|Date of Decision||28-Jan-2021|
|Date of Acceptance||18-May-2021|
|Date of Web Publication||19-May-2022|
Anand K Gudur
Department of Oncology, KIMSDU, Karad, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Datkhile KD, Gudur AK, Gudur RA, Bhosale SJ. A hospital-based cross-sectional study on assessment of ER, PR, and Her2 status in breast cancer patients from tertiary-care hospital of rural Maharashtra. Indian J Cancer 2022;59:144-8
|How to cite this URL:|
Datkhile KD, Gudur AK, Gudur RA, Bhosale SJ. A hospital-based cross-sectional study on assessment of ER, PR, and Her2 status in breast cancer patients from tertiary-care hospital of rural Maharashtra. Indian J Cancer [serial online] 2022 [cited 2022 Jun 27];59:144-8. Available from: https://www.indianjcancer.com/text.asp?2022/59/1/144/345489
Breast cancer (BC) is the most common malignant disease worldwide, accounting for 24% of new cancer cases and 15% of cancer deaths in 2018. BC has been ranked as the number one cancer among Indian women with an age-adjusted rate as high as 25.8 per 100,000 women and mortality of 12.7 per 100,000 women. There was an urban-rural divide in BC incidence and mortality, but the scenario is rapidly changing. Since cancer cervix incidence is decreasing, BC has surpassed it as the most common cancer in women even in rural India in the previous decade. In India, although the age-adjusted incidence rate of BC is lower (25.8 per 100,000) than in the United Kingdom (95 per 100,000) mortality is at par (12.7 versus 17.1 per 100,000) with the United Kingdom. This disparity in incidence compared with mortality may be explained due to young age at diagnosis, ignorance regarding screening and early symptoms, late stages at diagnosis, unavailability of cancer treatment facilities, and so on. Most of the data regarding cancer statistics in India come from hospital-based registries from the urban population. Rural India remains underrepresented in the national statistics. As major advances are happening in the diagnostic and therapeutic landscapes of BC, it is imperative that the characteristics of the disease in rural India be analyzed and compared with the rest of the country. To plan and formulate scientific cancer screening and treatment guidelines, we need correct and complete knowledge of epidemiology.
BC is a heterogeneous disease. Pathologic subtyping is accurately essential as both a prognostic and predictive marker. Invasive duct carcinoma (IDC) is the most common type accounting for 40% to 75%. IDC is again subdivided into many subtypes, IDC no specific type being the most common subtype. Invasive lobular carcinoma (ILC) is the second major biologically distinct invasive mammary carcinoma. It constitutes 5% to 15% of invasive breast carcinoma and usually affects older age-group women., Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (Her2) expression status has become an essential part of pathology since it is now proven that they have significant prognostic value. In the previous decade, many efforts have been concentrated to supplement the morphological classification of breast carcinoma with molecular parameters that can provide a clearer appreciation for the heterogeneity of BC and for better prediction of tumor behavior to improve therapeutic strategies. Perou et al. classified BCs into distinct subgroups based on similarities in the gene expression profiles using the microarray technology. This classification gives significantly better insights into tumor biology, hence assisting in improved decision-making. Hence, this study was aimed at collating the data of BC cases presenting to the oncology unit of Krishna Hospital and Medical Research Centre (KH and MRC) in the preceding 5 years to know the epidemiological and pathological characteristics. This will help in formulating BC management protocols for patients attending a tertiary-care hospital in rural management in the upcoming future.
In this hospital-based retrospective analysis, data of 350 BC patients diagnosed with primary invasive breast carcinomas and operated between June 2014 and July 2019 in the Department of Oncology of KH and MRC of Krishna Institute of Medical Sciences were included. Metastatic BC at presentation was excluded from the analysis. The primary histological diagnosis was performed on paraffin-embedded breast tissue blocks fixed in neutral buffered formalin. Immunohistochemistry was performed for ER, PR, and Her2 status. The clinicopathological parameters, including age at presentation, the menopausal status of the patient, histological type, tumor grade, tumor size, axillary lymph nodes involved, and ER/PR/Her2 status, were noted and the data were analyzed. Informed consent was obtained from all participants, and the study protocol was approved by the Institutional Ethics Committee. Statistical analysis was performed in Microsoft Excel where the data was entered in a Microsoft Excel spreadsheet from Microsoft Windows 10 and presented as mean ± standard deviation. The difference between the subgroups based on the status of ER/PR/Her2 and the median age, menopausal status, tumor size, and lymph nodes status were evaluated by one-way analysis of variance. Chi-square test was used to analyze the associations between classic clinicopathological parameters (histological type and tumor grade) and combined ER/PR status. A P value < 0.001 was considered statistically significant.
| » Discussion|| |
Women patients ≥18 years of age with invasive primary BC Stages I to III were included in this study. Metastatic cases were excluded. A total of 350 cases were studied. The clinicopathological characteristics in BC patients are represented in [Table 1]. The median age at presentation was 50 years, with age at presentation in the range of 23 to 90 years. A total of 17.72% of patients were below the age of 40 years. Among 350 patients, 155 cases (44.29%) were premenopausal compared with 195 cases (55.71%) who were postmenopausal; 22.57% of patients underwent breast conservation surgery (wide-excision right breast 12%; left breast 10.57%) compared with 77.43% of patients who underwent modified radical mastectomy (right breast 35.71%; left breast 41.72%). The mean number of lymph nodes extracted was 8.36 ± 6.10 with a range of 4 to 38. Most of the tumors were left sided (i.e. 52.29%), whereas 47.71% involved the right breast. The tumor size ranged from 0.4 to 6.5 cm with a mean range of 2.50 ± 1.17 cm; 44.29% tumors were less than 2 cm and 55.71% tumors more than 2 cm. The most frequent histological type of cancer was IDC with 85.43% followed by invasive medullary carcinoma (5.71%). Other types included ILC (2.29%), mucinous carcinoma (2.86%), invasive apocrine carcinoma (2.00%), and other miscellaneous types (1.71%; neuroendocrine carcinoma, tubular carcinoma, and carcinosarcoma). With respect to the Bloom–Richardson grade of the disease, 26% were Grade I and 27.71% were Grade II, whereas most of the tumors (162; 46.29%) were of Grade III [Table 1]. In the present study, when we correlated the hormone receptor status, including, ER, PR, and Her2 among 350 BC cases with their clinical and pathological features, we demonstrated the following findings: 55.14% cases were ER positive, 51.43% cases were PR positive, and 14.57% cases were positive for Her2. [Table 2] summarizes ER, PR, and Her2 expression status and its correlation with other clinicopathological features. A total of 168 (48%) cases were ER, PR positive, and Her2 negative; 116 (33.14%) cases showed triple-negative tumors, whereas only 9 (2.57%) cases tumors showed expression of all the three markers, that is, ER, PR, and Her2. The distribution pattern of hormone receptors (ER, PR, and Her2) in the breast tumor tissue is represented in [Figure 1]. When we compared combined ER, PR, and Her2 with other groups, ER/PR-positive and Her2-negative tumors were more frequent, that is, 48% cases followed by triple-negative tumors in 33.14% cases [Table 2]. The median age at presentation in triple-negative breast cancer (TNBC) was 48 years, whereas for the rest of the patients, the median age was 52 years. Triple-negative tumors were more frequent in premenopausal patients (55.17%) compared with postmenopausal patients (44.83%), but this was not statistically significant [Table 3]. There are very few studies to explore the correlation between ER, PR, and Her2 status with other prognostic factors such as age, menopausal status, histological type, tumor size, axillary lymph node status, and so on, from the BC patients of the southwestern part of Maharashtra. Several significant observations could be made from our study. The median age at diagnosis was significantly lower in India compared with the Western population. This finding was confirmed in our data also with the median age at diagnosis being 50 years. Also, 17.72% of the cases were below the age of 40 years, compared with the Western literature where significantly fewer patients belong to this age-group., This finding corroborates with the findings of a large population-based registry survey by Bidoli et al. in which a higher frequency of early onset BCs in women was observed in low- and middle-income countries than in the high-income countries. This may represent the median age of population in these countries is lower than that in the developed countries. But this alone may not explain the rising absolute numbers of early onset BCs, and a need to change the age criteria in the screening policies may be urgently required., The earlier age at diagnosis can also be attributed and gets complicated by the fact that the number of TNBC in our country is higher compared with the rest of the world. In our series, 33.14% of cases were TNBC compared with 11.2% in the study by Dent et al. Also, the median age at diagnosis in patients with TNBC was much lower at 48 years in our study compared with the majority of findings from developed countries. As per a large population-based study regarding the global trends of BC, around 40% of cases belonged to the premenopausal age-group in south and central Asian countries in contrast with as low as around 20% in few developed countries in America and Europe. We had 44.29% patients in the premenopausal age-group [Table 1]. Pathological features such as type, stage, and grade of disease were similar to other published data in India. In our cases, 14.57% were positive for Her2. Her2 is normally overexpressed in 20% to 25% of BCs worldwide. Overexpression of Her2 is an indicator of poorer prognosis, but these patients will benefit from multiple Her2-targeted therapies. We demonstrated a higher percentage of ER (55.14%) and PR (51.43%) positivity [Table 2]. When we study the ER/PR expression in other Indian studies, the positivity of ER/PR from western India showed 25%, a study from southern India showed 47.6%, northern India showed 16.6%, and eastern India showed 37.92%. Hormone receptor expression status is one of the most important prognostic and predictive markers, with ER/PR-positive tumors having better disease-free survival and overall survival compared with triple-negative tumors. Although there was a trend of TNBC being more common in premenopausal patients as compared with ER/PR-positive disease being more common in postmenopausal patients, this difference was not statistically significant. Thus, the study conducted in women residing in rural Maharashtra explored the correlation between hormone receptor status and clinicopathological variables. These data help to add information and form management protocols for BC in the region, since BC is fast becoming a major health concern even in rural parts of the country. Thus, BC is increasing in incidence in India. It affects younger patients and is usually more aggressive compared with the Western counterpart. Therefore, screening protocols in the age-group of 40 to 49 years need immediate attention and rethinking.
|Figure 1: Representative immunohistochemical staining images showing positivity of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2). a, b, c showing triple negative; d, e, f showing positive staining for ER, PR, and Her2; g, h, i showing positive staining for ER, PR, and negative staining for Her2; and j, k, l showing ER, PR-negative and -positive staining for Her2 (original magnification 10×)|
Click here to view
|Table 1: Frequency distribution of Clinicopathological characteristics in breast cancer patients|
Click here to view
|Table 2: Distribution of hormone receptors (ER/PR/Her2) in breast cancer patients|
Click here to view
|Table 3: Relationship between hormone receptor (ER/PR/Her2) status with age, menopausal status, histological type, tumor size, and lymph node status in breast cancer patients|
Click here to view
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent. In the form the patient(s) has/have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
The authors acknowledge Krishna Institute of Medical Sciences “Deemed to be University” for providing access to all the facilities.
Financial support and sponsorship
This study was supported by Intramural Funding (KIMSDU, Karad).
| » References|| |
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
Malvia S, Bagadi SA, Dubey US, Saxena S. Epidemiology of breast cancer in Indian women. Asia Pac J Clin Oncol 2017;13 289-95.
Babu GR, Lakshmi SB, Thiyagarajan JA. Epidemiological correlates of breast cancer in South India. Asian Pac J Cancer Prev 2013;14:5077-83.
Gupta A, Shridhar K, Dhillon PK. A review of breast cancer awareness among women in India: Cancer literate or awareness deficit? Eur J Cancer 2015;51:2058-66.
Farid M. Essentials of Diagnostic Breast Pathology, Practical Approach. 1st
ed. Berlin: Springer; 2007.
Makki J. Diversity of breast carcinoma: Histological subtypes and clinical relevance. Clin Med Insights Pathol 2015;8:23-31.
Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al
. Molecular portraits of human breast tumours. Nature 2000;406:747-52.
Rangarajan B, Shet T, Wadasadawala T, Nair NS, Sairam M, Hingmire SS, et al
. Breast cancer: An overview of published Indian data. South Asian J Cancer 2016;5:86-92.
] [Full text]
Anders CK, Johnson R, Litton J, Phillips M, Bleyere A. Breast cancer before age 40 years. Semin Oncol 2009;36:237-49.
Desantis C, Ma J, Bryan L, Jemal A. Breast cancer statistics, 2013. CA Cancer J Clin 2014;64:52-62.
Bidoli E, Virdone S, Hamdi-Cherif M, Toffolutti F, Taborelli M, Panato C, et al
. Worldwide age at onset of female breast cancer: A 25-year population-based cancer registry study. Sci Rep 2019;9:14111.
World Health Organization. Screening for Breast Cancer. Geneva: WHO; 2009.
US Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009;151:716-26.
Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al
. Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin Cancer Res 2007;13:4429-34.
Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: A population-based study from the California Cancer Registry. Cancer 2007;109:1721-8.
Heer E, Harperb A, Ascandor N, Sung H, McCormack V, Fidler-Benaoudia MM. Global burden and trends in premenopausal and postmenopausal breast cancer: A population-based study. Lancet Glob Health 2020;8:1027-37.
Wang J, Xu B. Targeted therapeutic options and future perspectives for HER2-positive breast cancer. Signal Transduct Target Ther 2019;4:34-56.
Desai SB, Moonim MT, Gill AK, Punia RS, Naresh KN, Chinoy RF. Hormone receptor status of breast cancer in India: A study of 798 tumors. Breast 2000;9:267-70.
Patnayak R, Jena A, Rukmangadha N, Chowhan A, Sambhasivaiah K, Phaneendra B, et al
. Hormone receptor status (estrogen receptor, progesterone receptor), human epidermal growth factor-2 and p53 in South Indian breast cancer patients: A tertiary care center experience. Indian J Med Paediatr Oncol 2015;36:117-22.
] [Full text]
Kaul R, Sharma J, Minhas SS, Mardi K. Hormone receptor status of breast cancer in the Himalayan region of Northern India. Ind J Surgery 2011;73:9-12.
Chatterjee K, Bhaumik G, Chattopadhyay B. Estrogen receptor and progesterone receptor status of breast cancer patients of eastern India: A multi-institutional study. South Asian J Cancer 2018;7:5-6.
] [Full text]
Onitilo AA, Engel JM, Greenlee RT, Mukesh BN. Breast cancer subtypes based on ER/PR and Her2 expression: Comparison of clinicopathological features and survival. Clin Med Res 2009;7:4-13.
[Table 1], [Table 2], [Table 3]